TRKing down an old oncogene in a new era of targeted therapy

Cancer Discov. 2015 Jan;5(1):25-34. doi: 10.1158/2159-8290.CD-14-0765. Epub 2014 Dec 19.


The use of high-throughput next-generation sequencing techniques in multiple tumor types during the last few years has identified NTRK1, 2, and 3 gene rearrangements encoding novel oncogenic fusions in 19 different tumor types to date. These recent developments have led us to revisit an old oncogene, Trk (originally identified as OncD), which encodes the TPM3-NTRK1 gene fusion and was one of the first transforming chromosomal rearrangements identified 32 years ago. However, no drug has yet been approved by the FDA for cancers harboring this oncogene. This review will discuss the biology of the TRK family of receptors, their role in human cancer, the types of oncogenic alterations, and drugs that are currently in development for this family of oncogene targets.

Significance: Precision oncology approaches have accelerated recently due to advancements in our ability to detect oncogenic mutations in tumor samples. Oncogenic alterations, most commonly gene fusions, have now been detected for the genes encoding the TRKA, TRKB, and TRKC receptor tyrosine kinases across multiple tumor types. The scientific rationale for the targeting of the TRK oncogene family will be discussed here.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Molecular Targeted Therapy
  • Multigene Family
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Oncogene Proteins / antagonists & inhibitors
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism*
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use


  • Antineoplastic Agents
  • Oncogene Proteins
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • oncogene protein trk